The overall objective of this proposal addresses itself to the analysis of specific gene interactions between the host and viral genomes in differentiation and neoplastic transformation. The pathogenesis of leukemia is an intricate process and a number of preconditions must be satisfied in order for the disease to occur and run its course. Studies involving murine model systems and murine leukemia viruses (MuLV) have proven invaluable in revealing some of the complexities involved. Recently, we have identified and characterized a recombinant inbred (RI) mouse strain, designated BXH-2, which spontaneously produces a B-tropic MuLV throughout life and has a high incidence of nonthymic leukemia (89% die of leukemia at less than one year of age). Also, unlike other high leukemia inbred strains, about one-third of the leukemia-affected females in the BXH-2 strain develop a posterior paralysis. The BXH-2 strain was the only BXH-strain among thirteen, generated by crossing two low leukemic strains (C57BL/6J x C3H/HeJ), to have a high incidence of leukemia, thus one is presented with a disease model and twelve genotypically distinct controls. In this respect we feel that BXH-2 mice represent an important new model system for studying both host and viral factors involved in neoplastic disease. Specifically, utilizing BXH-2 RI mice, we propose to: (1) identify and quantitate the MuLVs present in tissues of BXH-2 mice both as a function of age and disease state, (2) identify the target cell of BXH-2 leukemia using lymphoid cell surface markers and in vitro culturing techniques, (3) determine the oncogenic potential and tissue specificities of the BXH-2 viral isolates, (4) quantitate the amount of MuLV proviral sequences present in normal and tumorous tissues of BXH-2 mice by reassociation kinetics, utilizing radiolabeled probes specific for ecotropic and xenotropic DNA sequences, (5) determine if the paralytic disease observed in some BXH-2 leukemic mice is transmissible to other newborn mice by intracranial inoculation, and (6) study the relationship between immune responsiveness and leukemogenesis in BXH-2 mice by evaluating their ability to mount an immune response.